ABSTRACT
ABC transporters (ATP-binding cassette transporter) traffic drugs and their metabolites across membranes, making ABC transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging because they are large and low-abundance transmembrane proteins. Here, we analysed 200 samples of crude and membrane-enriched fractions from human liver, kidney, intestine, brain microvessels and skin, by label-free quantitative mass spectrometry. We identified 32 (out of 48) ABC transporters: ABCD3 was the most abundant in liver, whereas ABCA8, ABCB2/TAP1 and ABCE1 were detected in all tissues. Interestingly, this atlas unveiled that ABCB2/TAP1 may have TAP2-independent functions in the brain and that biliary atresia (BA) and control livers have quite different ABC transporter profiles. We propose that meaningful biological information can be derived from a direct comparison of these data sets.
Subject(s)
ATP-Binding Cassette Transporters/analysis , ATP-Binding Cassette Transporters/chemistry , Brain/metabolism , Intestinal Mucosa/metabolism , Kidney/metabolism , Liver/metabolism , Skin/metabolism , ATP-Binding Cassette Transporters/metabolism , Adolescent , Adult , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Male , Mass Spectrometry , Organ SpecificityABSTRACT
BACKGROUND: Drug safety has major implications for patients' lives. However, this concept is still considered new to some healthcare professionals. OBJECTIVE: This study aims to investigate the knowledge and awareness of Saudi healthcare professionals to pharmacovigilance (PV). Setting Governmental and private hospitals at three main cities in Saudi Arabia (Riyadh, Jeddah, and Dammam). METHODS: A cross-sectional survey among healthcare professionals (pharmacists, physicians, and nurses) within 12 Saudi hospitals was conducted between November and December 2012. The questionnaire consisted of 18 questions assessing the knowledge, awareness, and attitude of healthcare professionals (HCPs) towards science and the concept of PV. Descriptive statistics were used to analyze the data. The data were analyzed using Statistical Analysis Software (SAS 9.3). Main outcome measure Knowledge, attitude and practice of HCPs toward pharmacovigilance. RESULTS: Three-hundred and thirty-two healthcare professionals completed the survey (response rate 72 %), 110 (34 %) physicians, 106 (33 %) pharmacists, and 104 (32 %) nurses. More than half of the participants (55 %) did not know the correct definition of PV. Two-thirds of the respondents, 207 (65.5 %), had knowledge of the aim of post-marketing surveillance, yet only 113 (36.9 %) were aware that the National Pharmacovigilance and Drug Safety Center is the official body for monitoring adverse drug reaction in Saudi Arabia. In addition, 34.7 % agreed that lack of time could be a major barrier for reporting. The majority of the respondents (78.4 %) believed that reporting was a professional obligation and hospitals should have a drug safety department. CONCLUSIONS: There was a limited knowledge of pharmacovigilance that could have affected reporting incidence. Educational intervention and a practical training program need to be applied by the drug regulatory body as well as health authorities to enhance the pharmacovigilance and drug safety culture in Saudi Arabia.
